%0 Journal Article
%T In vivo-stable bis-iminobiotin for targeted radionuclide delivery with the mutant streptavidin.
%A Tatsumi T
%A Zhao S
%A Kasahara A
%A Aoki M
%A Nishijima KI
%A Ukon N
%A Kodama T
%A Takahashi K
%A Sugiyama A
%A Washiyama K
%A Yamatsugu K
%A Kanai M
%J Bioorg Med Chem Lett
%V 108
%N 0
%D 2024 Aug 1
%M 38777280
%F 2.94
%R 10.1016/j.bmcl.2024.129803
%X Targeted delivery of radionuclides to tumors is significant in theranostics applications for precision medicine. Pre-targeting, in which a tumor-targeting vehicle and a radionuclide-loaded effector small molecule are administered separately, holds promise since it can reduce unnecessary internal radiation exposure of healthy cells and can minimize radiation decay. The success of the pre-targeting delivery requires an in vivo-stable tumor-targeting vehicle selectively binding to tumor antigens and an in vivo-stable small molecule effector selectively binding to the vehicle accumulated on the tumor. We previously reported a drug delivery system composed of a low-immunogenic streptavidin with weakened affinity to endogenous biotin and a bis-iminobiotin with high affinity to the engineered streptavidin. It was, however, unknown whether the bis-iminobiotin is stable in vivo when administered alone for the pre-targeting applications. Here we report a new in vivo-stable bis-iminobiotin derivative. The keys to success were the identification of the degradation site of the original bis-iminobiotin treated with mouse plasma and the structural modification of the degradation site. We disclosed the successful pre-targeting delivery of astatine-211 (211At), α-particle emitter, to the CEACAM5-positive tumor in xenograft mouse models.